Íbias Javier, O'Dell Laura E, Nazarian Arbi
Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA.
Department of Psychology, University of Texas at El Paso, El Paso, TX, USA.
Behav Brain Res. 2018 Oct 1;351:75-82. doi: 10.1016/j.bbr.2018.05.018. Epub 2018 May 24.
The rewarding effects of nicotine have been previously shown to be enhanced in rodent models of diabetes. It is presently unclear whether the enhanced nicotine reward observed in the diabetes models are mediated via an insulin or glucose mechanism. This study examined whether the enhanced rewarding effects of nicotine observed in streptozotocin (STZ)-treated rats are insulin-mediated. Male and female rats were treated with STZ and the rewarding effects of nicotine (0.2 mg/kg) were measured using the conditioned place preference (CPP) procedure. Some STZ-treated animals received insulin supplementation via subcutaneous pellets immediately after STZ administration, while other rats received daily injections of dapagliflozin (10 mg/kg), a sodium-glucose cotransporter-2 inhibitor. Both male and female STZ-treated rats displayed hyperglycemia, and their blood glucose levels (BGLs) were normalized to control levels following insulin supplementation or dapagliflozin administration. STZ-treated male rats displayed higher nicotine CPP relative to vehicle-treated controls. This effect was abolished in rats that received insulin supplementation or dapagliflozin administration. STZ-treated female rats displayed reduced levels of nicotine CPP as compared to male rats, regardless of treatment condition. These results suggest that glucose plays a major role in modulating the rewarding effects of nicotine in male rats treated with STZ.
尼古丁的奖赏效应先前已在糖尿病啮齿动物模型中显示增强。目前尚不清楚在糖尿病模型中观察到的尼古丁奖赏增强是否通过胰岛素或葡萄糖机制介导。本研究考察了在链脲佐菌素（STZ）处理的大鼠中观察到的尼古丁奖赏增强效应是否由胰岛素介导。雄性和雌性大鼠接受STZ处理，并使用条件性位置偏爱（CPP）程序测量尼古丁（0.2mg/kg）的奖赏效应。一些STZ处理的动物在给予STZ后立即通过皮下植入物补充胰岛素，而其他大鼠每天注射达格列净（10mg/kg），一种钠-葡萄糖协同转运蛋白2抑制剂。接受STZ处理的雄性和雌性大鼠均出现高血糖，在补充胰岛素或给予达格列净后，它们的血糖水平（BGLs）恢复至对照水平。与接受载体处理的对照相比，接受STZ处理的雄性大鼠表现出更高的尼古丁CPP。在接受胰岛素补充或达格列净给药的大鼠中，这种效应被消除。无论治疗条件如何，接受STZ处理的雌性大鼠与雄性大鼠相比，尼古丁CPP水平降低。这些结果表明，葡萄糖在调节接受STZ处理的雄性大鼠中尼古丁的奖赏效应方面起主要作用。
